Background: The virulence of Plasmodium falciparum is associated with the capacity of the infected red blood cell (iRBC) to adhere to uninfected RBCs, a process known as rosetting, which has been linked to the occurrence of severe malaria. The present study was carried out in three Ethiopian malaria endemic localities to investigate the relationship between blood group type and severe disease in falciparum malaria. Methods: A total of 210 cases of malaria (70 severe and 140 uncomplicated) and 190 healthy controls participated in the study. Patients with at least one of the severe malaria syndromes (cerebral malaria, severe anaemia and circulatory collapse) were considered as severe malaria cases. Results: In the severe malaria category, there were 25 (35.7%), 15 (21.4%), 14 (20%) and 16 (22.9%) blood group A, B, AB and O patients, respectively. Blood group O was the dominant blood type in both uncomplicated malaria (45.7%) and healthy controls (41.6%). A case of severe malaria was almost twice as likely to be of type A as to be of type O (odds ratio (OR) 0.42, 95 % confidence interval (CI) 0.20-0.88, P = 0.019), and more than twice as likely to be of type B as to be of type O (OR 0.38, 95 % CI 0.16-0.89, P = 0.02). Furthermore, individuals with severe malaria were about six fold less likely to be of O as to be of type AB (OR 0.19, 95 % CI 0.07-0.51, P = 0.0005). Conclusion: The study revealed that on the basis of the three criteria (cerebral malaria, severe anaemia an
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